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慢性无机汞暴露诱导中枢 TNFα 表达的性别特异性变化:与自闭症有关?

Chronic inorganic mercury exposure induces sex-specific changes in central TNFα expression: importance in autism?

机构信息

Department of Pharmacology/Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107, United States.

出版信息

Neurosci Lett. 2011 Oct 17;504(1):40-4. doi: 10.1016/j.neulet.2011.08.053. Epub 2011 Aug 31.

Abstract

Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer's disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain neuropathologies (i.e., autism). Furthermore, mounting evidence points to the involvement of glial activation in autism. Therefore, we utilized an in vivo model to assess the effects of mercury exposure on neuroimmune signaling. In prairie voles, 10 week mercury exposure (60ppm HgCl(2) in drinking water) resulted in a male-specific increase in TNFα protein expression in the cerebellum and hippocampus. These findings are consistent with our previously reported male-specific mercury-induced deficits in social behavior and further support a role for heavy metals exposure in neuropathologies such as autism. Subsequent studies should further evaluate the mechanism of action and biological consequences of heavy metals exposure. Additionally, these observations highlight the potential of neuroimmune markers in male voles as biomarkers of environmental mercury toxicity.

摘要

汞具有神经毒性,越来越多的证据表明,环境暴露于汞可能导致包括阿尔茨海默病和自闭症谱系障碍在内的神经病理学。汞已知会破坏外周的免疫能力,然而,对于汞对神经免疫信号的影响知之甚少。鉴于汞暴露和神经炎症都与某些神经病理学(即自闭症)有关,汞对中枢免疫功能的影响可能非常重要。此外,越来越多的证据表明胶质细胞激活参与了自闭症。因此,我们利用体内模型来评估汞暴露对神经免疫信号的影响。在草原田鼠中,10 周的汞暴露(饮用水中 60ppm HgCl2)导致小脑和海马中的 TNFα 蛋白表达出现雄性特异性增加。这些发现与我们之前报道的雄性特异性汞诱导的社会行为缺陷一致,并进一步支持重金属暴露在自闭症等神经病理学中的作用。后续研究应进一步评估重金属暴露的作用机制和生物学后果。此外,这些观察结果强调了雄性田鼠神经免疫标志物作为环境汞毒性生物标志物的潜力。

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